Increased platelet arachidonic acid metabolism in diabetes mellitus.
Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. This study sought to determine if platelet obtained from insulin-dependent diabetic subjects synthesize increased quantities of the labile aggregating substance, thromboxane A2 (TXA2), and if it may play a role in the enhanced platelet aggregation. Arachidonic acid (1 mM)-stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (P less than 0.01, N = 12) in platelet-rich plasma obtained from diabetics compared with matched controls. Arachidonic acid-stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, P less than 0.02, N = 15). Platelet aggregation induced by arachidonic acid (0.4-0.8 mM) was inhibited significantly less by 13-azaprostanoic acid (P less than 0.04, N = 14), a competitive antagonist of the actions of prostaglandin H2 or TXA2 on platelets, compared with matched controls. The results support the notion that platelets obtained from some insulin-dependent diabetic subjects manifest increased synthesis of TXA2, which may contribute to the enhanced platelet aggregation.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood* / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010974:Platelet Aggregation / Q000187:drug effects; D011466:Prostanoic Acids / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
D001095:Arachidonic Acids; D001786:Blood Glucose; D011466:Prostanoic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; C022574:13-azaprostanoic acid; D004837:Epinephrine